Thymocyte death by neglect: contribution of engulfing macrophages

European Journal of Immunology
Z SzondyKrisztina Köröskényi

Abstract

The thymus provides the microenvironment in which thymocytes develop into mature T cells, and interactions with thymic stromal cells are thought to provide the necessary signals for thymocyte maturation. Recognition of self-MHC by T cells is a basic requirement for mature T-cell functions, and those thymocytes that do not recognize the peptide-loaded self-MHC molecules found in the thymus, and therefore lack a TCR signal, undergo a default death pathway named "death by neglect" in the thymic cortex. In the absence of this TCR signaling, it has been suggested that binding of glucocorticoids to - or the ligation of certain cell surface molecules, such as CD8, CD24, CD45, or CD99 on - these neglected thymocytes will induce them to enter the apoptotic program. Apoptotic thymocytes are cleared by the surrounding macrophages and, as a consequence, these macrophages are known to release various molecules, such as adenosine, retinoids, TGF-β, ATP, and carbon monoxide. Interestingly, all these molecules have been described to induce or promote apoptosis in thymocytes in the absence of TCR signaling. Here, we propose that thymic macrophages, because they continually engulf apoptotic cells, might constantly provide these cell death-induci...Continue Reading

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Citations

May 15, 2015·Journal of Immunology Research·Ebzadrel Carbajal-FrancoGloria Soldevila
Mar 14, 2017·PLoS Computational Biology·Julien Vibert, Véronique Thomas-Vaslin
Jan 10, 2018·Frontiers in Pharmacology·Krisztina KöröskényiZsuzsa Szondy
Jan 11, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rachael L PhilipsVirginia S Shapiro
Sep 21, 2013·Journal of Leukocyte Biology·Virginia MainaAnna Villa

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis